The primary biological function of human growth hormone (hGH) includes stimulating growth, cell repair, and regeneration. Once the primary growth period of adolescence concludes, the primary function of hGH in adulthood becomes that of cell regeneration and repair, helping regenerate skin, bones, heart, lungs, liver, and kidneys to their optimal, youthful cell levels. As is the case with many of our other hormones or their precursors, such as testosterone, estrogen, progesterone, DHEA, and melatonin, hGH levels decline with age. Therapeutically, many of these hormones can be replaced to offset some of the effects of aging such as menopausal symptoms in women or erectile dysfunction in men. Additionally, hGH and testosterone affect sterility and fertility in animals, including human beings.
The human body, like every other living entity, works on daily, or circadian, as well as monthly and annual rhythms. Daily growth hormone secretion diminishes with age with roughly half the levels at age 40 that we had when we were 20, and about one-third of those youthful levels at age 60. In some 60-year-olds, the levels are as low as 25% of the hGH levels in a 20-year-old. Symptoms of aging include loss of muscle, increase of fat, decreased physical mobility, decreased energy levels, and as a result, diminished socialization, diminished healing ability, and an increased risk of cardiovascular disease and decreased life expectancy. Low hGH levels are associated with the aging process and early onset of disease. For example, Rosen and Bengtsson noted an increased death rate from cardiovascular disease in hGH deficient patients. (Rosen, T., Bengtsson, B. A., Lancet 336 (1990): 285-2880)
Low hGH has been shown to decrease fertility in humans. See, e.g., Homburg, R., A. Singh, et al. (2012), “The re-growth of growth hormone in fertility treatment: a critical review.” Hum Fertil (Camb) 15(4): 190-193; Giampietro, A., D. Milardi, et al. (2009), “The effect of treatment with growth hormone on fertility outcome in eugonadal women with growth hormone deficiency: report of four cases and review of the literature.” Fertil Steril 91(3): 930 e937-911; Kalra, S., B. Kalra, et al. (2008), Growth hormone improves semen volume, sperm count and motility in men with idopathic normogonadotropic infertility. 10th European Congress of Endocrinology. Berlin, Germany, Endocrine Abstracts. 16: P613; Karaca, Z. and F. Kelestimur (2011), “Pregnancy and other pituitary disorders (including hGH deficiency).” Best Pract Res Clin Endocrinol Metab 25(6): 897-910; Magon, N., S. Singh, et al. (2011), “Growth hormone in male infertility.” Indian J Endocrinol Metab 15 Suppl 3: S248-249; and Sakai, S., T. Wakasugi, et al. (2011), “Successful pregnancy and delivery in a patient with adult hGH deficiency: role of hGH replacement therapy.” Endocr J 58(1): 65-68, the contents of each of which are incorporated herein by reference.
Until recently, hGH was available only in expensive injectable forms, and benefits from the restoration of hGH levels available only to those with the ability to pay. Most recently substances that can trigger the release of human growth hormone from an individual's own anterior pituitary gland have become available. These are generically referred to as secretagogues. Secretagogues have the ability to restore hGH levels, potentially to the levels found in youth. See, e.g., “Grow Young With hGH” by Dr. Ronald Klatz, President of the American Academy of Anti-Aging, published in 1997 by Harper Collins.
HGH-deficient adults have marked reductions in lean body mass, and within months of hGH treatment, gains in lean body mass, skin thickness, and muscle mass are observed. (Cuneo R C et al. J Appl Physiol 1991; 70:695-700; Cuneo R C et al. J Appl Physiol 1991; 70:688-694; Rudman D et al. N Engl J Med 1969; 280:1434-1438)
It is well-established that intravenous (IV) administration of some amino acids results in significant hGH secretion. Intravenous infusion of 183 mg of arginine/kg body weight in females increased hGH levels >20-fold, and 30 g of arginine elevated serum hGH levels 8.6 fold in males. (Merimee T J et al. N Engl J Med 1969; 280:1434-1438; Alba-Roth J et al. J Clin Endocrinol Metab 1988; 67:1186-1189) Other amino acids, such as methionine, phenylalanine, lysine, histidine, and ornithine, have also led to marked increases in hGH. (Alba-Roth, Muller, Schopohl, & von Werder, 1988; Chromiak & Antonio, 2002; Gourmelen, M., M. Donnadieu, et al. (1972) Ann Endocrinol (Paris) 33(5): 526-528)
Given the difficulties in IV administration of amino acids for widespread use, interest in elucidating the hGH response to oral amino acid supplements prompted testing of such supplements containing mainly arginine, lysine, and ornithine at varying amounts. Yet the pronounced variability in results among these studies makes clear the complexities involved in the design of an effective supplement for supporting hGH levels in the general public. (Suminski R R et al. Int J Sport Nutr 1997; 7:48-60; Lambert M I et al. Int J Sport Nutr 1993; 3:298-305; Corpas E et al. J Gerontol 1993; 48:M128-M133; Isidori A et al. Curr Med Res Opin 1981; 7:475-481; Fogelholm G M et al. Int J Sport Nutr 1993; 3:290-297; Chromiak J A, Antonio J. Nutrition 2002 July; 18(7-8):657-61)
Serum hGH levels differ in relation to various factors including age, gender, hormone status, and BMI. (Iranmanesh, Lizarralde, & Veldhuis, 1991); (Chowen, Frago, & Argente, 2004) Growth hormone has been shown to be important in multiple stages of pregnancy including early antral follicle recruitment, subsequent follicular growth, and oocyte maturation. Moreover, administration of growth hormone during the ovarian stimulation phase of in vitro fertilization (IVF) cycles has been shown to increase the probability of clinical pregnancy.